TY - JOUR
T1 - Activation-induced cytidine deaminase is dispensable for virus-mediated liver and skin tumor development in mouse models
AU - Nguyen, Tung
AU - Xu, Jianliang
AU - Chikuma, Shunsuke
AU - Hiai, Hiroshi
AU - Kinoshita, Kazuo
AU - Moriya, Kyoji
AU - Koike, Kazuhiko
AU - Marcuzzi, Gian Paolo
AU - Pfister, Herbert
AU - Honjo, Tasuku
AU - Kobayashi, Maki
N1 - Funding Information:
Ministry of Education, Culture, Sports, Science and Technology of Japan Grant-in-Aid for Specially Promoted Research (17002015 to T.H.); Grant-in-Aid for Scientific Research (C) (25440007 to M.K.).
PY - 2014/7
Y1 - 2014/7
N2 - Activation-induced cytidine deaminase (AID) not only promotes immune diversity by initiating somatic hypermutation and class switch recombination in immunoglobulin genes but also provokes genomic instability by introducing translocations and mutations into non-immunoglobulin genes. To test whether AID is essential for virus-induced tumor development, we used two transgenic tumor models: mice expressing hepatitis C virus (HCV) core proteins (HCV-Tg), driven by the hepatitis B virus promoter, and mice expressing human papillomavirus type 8 proteins (HPV8-Tg), driven by the Keratin 14 promoter. Both strains were analyzed in the absence and presence of AID by crossing each with AID-/- mice. There was no difference in the liver tumor frequency between the HCV-Tg/AID+/+ and HCV-Tg/AID-/- mice at 20 months of age although the AID+/+ mice showed more severe histological findings and increased cytokine expression. Furthermore, a low level of AID transcript was detected in the HCV-Tg/AID+/+ liver tissue that was not derived from hepatocytes themselves but from intra-hepatic immune cells. Although AID may not be the direct cause of HCVinduced oncogenesis, AID expressed in B cells, not in hepatocytes, may prolong steatosis and cause increased lymphocyte infiltration into HCV core protein-induced liver lesions. Similarly, there was no difference in the time course of skin tumor development between the HPV8-Tg/AID-/- and HPV8-Tg/AID+/+ groups. In conclusion, AID does not appear to be required for tumor development in the two virus-induced tumor mouse models tested although AID expressed in infiltrating B cells may promote inflammatory reactions in HCV core protein-induced liver pathogenesis.
AB - Activation-induced cytidine deaminase (AID) not only promotes immune diversity by initiating somatic hypermutation and class switch recombination in immunoglobulin genes but also provokes genomic instability by introducing translocations and mutations into non-immunoglobulin genes. To test whether AID is essential for virus-induced tumor development, we used two transgenic tumor models: mice expressing hepatitis C virus (HCV) core proteins (HCV-Tg), driven by the hepatitis B virus promoter, and mice expressing human papillomavirus type 8 proteins (HPV8-Tg), driven by the Keratin 14 promoter. Both strains were analyzed in the absence and presence of AID by crossing each with AID-/- mice. There was no difference in the liver tumor frequency between the HCV-Tg/AID+/+ and HCV-Tg/AID-/- mice at 20 months of age although the AID+/+ mice showed more severe histological findings and increased cytokine expression. Furthermore, a low level of AID transcript was detected in the HCV-Tg/AID+/+ liver tissue that was not derived from hepatocytes themselves but from intra-hepatic immune cells. Although AID may not be the direct cause of HCVinduced oncogenesis, AID expressed in B cells, not in hepatocytes, may prolong steatosis and cause increased lymphocyte infiltration into HCV core protein-induced liver lesions. Similarly, there was no difference in the time course of skin tumor development between the HPV8-Tg/AID-/- and HPV8-Tg/AID+/+ groups. In conclusion, AID does not appear to be required for tumor development in the two virus-induced tumor mouse models tested although AID expressed in infiltrating B cells may promote inflammatory reactions in HCV core protein-induced liver pathogenesis.
KW - Hepatitis C virus
KW - Human papillomavirus type 8
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U2 - 10.1093/intimm/dxu040
DO - 10.1093/intimm/dxu040
M3 - Article
C2 - 24569264
AN - SCOPUS:84903634983
VL - 26
SP - 397
EP - 406
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 7
M1 - dxu040
ER -